Sj. Korsmeyer et al., Pro-apoptotic cascade activates BID, which oligomerizes BAK or BAX into pores that result in the release of cytochrome c, CELL DEAT D, 7(12), 2000, pp. 1166-1173
We review data supporting a model in which activated tBID results in an all
osteric activation of BAK, inducing its intramembranous oligomerization int
o a proposed pore for cytochrome c efflux, The BH3 domain of tBID is not re
quired for targeting but remains on the mitochondrial surface where it is r
equired to trigger BAK to release cytochrome c. tBID functions not as a por
e-forming protein but as a membrane targeted and concentrated death ligand,
tBID induces oligomerization of BAK, and both Bid and Bak knockout mice in
dicate the importance of this event in the release of cytochrome c. In para
llel, the full pro-apoptotic member BAX, which is highly homologous to BAK,
rapidly forms pores in liposomes that release intravesicular FITC-cytochro
me c similar to 20 Angstrom. A definable pore progressed from similar to 11
Angstrom consisting of two BAX molecules to a similar to 22 Angstrom pore
comprised of four BAX molecules, which transported cytochrome c. Thus, an a
ctivation cascade of pro-apoptotic proteins from BID to BAK or BAX integrat
es the pathway from surface death receptors to the irreversible efflux of c
ytochrome c.